Therapies for the bone in mucopolysaccharidoses.
Therapies for the bone in mucopolysaccharidoses.
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DOI：
10.1016/j.ymgme.2014.12.001
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发表时间：
2015-02
影响因子：
3.8
通讯作者：
Orii, Tadao
中科院分区：
文献类型：
--
作者：
Tomatsu, Shunji;Almeciga-Diaz, Carlos J.;Montatio, Adriana M.;Yabe, Hiromasa;Tanaka, Akemi;Vu Chi Dung;Giugliani, Roberto;Kubaski, Francyne;Mason, Robert W.;Yasuda, Eriko;Sawamoto, Kazuki;Mackenzie, William;Suzuki, Yasuyuki;Orii, Kenji E.;Barrera, Luis A.;Sly, William S.;Orii, Tadao
关键词：
粘多糖病（MPS）患者在多个组织中积累糖胺聚糖，可导致面部特征粗糙、智力迟钝、反复耳鼻感染、腹股沟和脐疝、肝脾肿大和骨骼畸形。与骨病变相关的临床特征可能包括明显的身材矮小、颈椎狭窄、胸突、肺小、关节僵硬（但MPS IV是松弛的）、脊柱后凸、腰椎和膝外翻。MPS患者通常需要坐轮椅，由于进行性骨骼发育不良、关节活动异常和骨关节炎，身体残疾随着年龄的增长而增加，导致1)上颈椎狭窄，2)限制性小肺，3)髋关节发育不良，4)关节活动受限，5)手术并发症。患者一生中通常需要进行多种骨科手术，包括颈椎减压融合、腕管松解、髋关节重建和置换术、股骨或胫骨截骨术。目前干预骨病进展的措施是不完善和姑息性的，迫切需要改进的治疗方法。酶替代疗法（ERT）、造血干细胞移植（HSCT）和基因疗法对于某些类型的MPS已经可用或正在开发中。输送足够的酶到骨骼，特别是无血管软骨，以防止或改善破坏性骨骼发育不良仍然是一个未满足的挑战。抗炎药的使用也在临床研究中。由于骨骼发育不良的严重程度与日常生活中的活动水平有关，因此治疗应在不可逆转的骨损伤和损伤之前的非常早期阶段开始。这篇综述阐述了目前的治疗方法及其对MPS骨病变的影响，包括ERT、HSCT、基因治疗和抗炎药物。
Patients with mucopolysaccharidoses (MPS) have accumulation of glycosaminoglycans in multiple tissues which may cause coarse facial features, mental retardation, recurrent ear and nose infections, inguinal and umbilical hernias, hepatosplenomegaly, and skeletal deformities. Clinical features related to bone lesions may include marked short stature, cervical stenosis, pectus carinatum, small lungs, joint rigidity (but laxity for MPS IV), kyphoscoliosis, lumbar gibbus, and genu valgum. Patients with MPS are often wheelchair-bound and physical handicaps increase with age as a result of progressive skeletal dysplasia, abnormal joint mobility, and osteoarthritis, leading to 1) stenosis of the upper cervical region, 2) restrictive small lung, 3) hip dysplasia, 4) restriction of joint movement, and 5) surgical complications. Patients often need multiple orthopedic procedures including cervical decompression and fusion, carpal tunnel release, hip reconstruction and replacement, and femoral or tibial osteotomy through their lifetime. Current measures to intervene in bone disease progression are not perfect and palliative, and improved therapies are urgently required. Enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), and gene therapy are available or in development for some types of MPS. Delivery of sufficient enzyme to bone, especially avascular cartilage, to prevent or ameliorate the devastating skeletal dysplasias remains an unmet challenge. The use of an anti-inflammatory drug is also under clinical study. Therapies should start at a very early stage prior to irreversible bone lesion, and damage since the severity of skeletal dysplasia is associated with level of activity during daily life. This review illustrates a current overview of therapies and their impact for bone lesions in MPS including ERT, HSCT, gene therapy, and anti-inflammatory drugs.
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影响因子：
12.4
作者：
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通讯作者：
Auricchio, Alberto
影响因子：
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作者：
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作者：
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影响因子：
3
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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